tbuckley/cabot-search huggingface dataset:
Creating patient-friendly informed consent form (ICF): Insights from global oncology patient insights panels (GOPIPs).
Authors: Dawn Aubel, Andrew Ciupek, Sydney Olshan, Zack Pemberton-Whiteley, Ali Stunt, Kristen Davis, Maria Piggin, M Claire Saxton, Anne Olshan, Alexey Salamakha, Fatima Cardoso, Ginny Mason
Journal: Journal of Clinical Oncology (2023)

e24199 Background: The informed consent form (ICF) provides patients with information to facilitate an informed decision about participation in a clinical trial. Legal and regulatory requirements, professional jargon and technical terms make ICFs long and complicated, creating barriers for patients to understand the participation requirements, which may lead to negative impact on recruitment and increased drop-out rates. Methods: Patient advocates with relevant knowledge of patient experiences in their respective disease areas were invited to review, edit, and provide recommendations for improving draft ICFs for company clinical trials to facilitate better understanding. These advocates are members of the Global Oncology Patient Insight Panels (GOPIPs), contracting with the company to provide the patient perspective along the clinical development continuum. The advocates received draft ICFs and completed a questionnaire regarding its readability, content, and formatting, or provided open-ended feedback. Researchers interviewed advocates to elicit in-depth responses and recommendations for improvement. A qualitative analysis was performed on all data collected to identify primary themes, which were incorporated into an internal guidance for clinical development teams, “Tips for Creating Patient-friendly ICFs: Insights from Global Oncology Patient Insights Panels (GOPIPs) 2018-2022.” Results: 36 draft ICFs for clinical trials were reviewed by 47 advocates in 13 hematology/oncology disease areas and 14 countries between 2018 and 2022. Qualitative analysis identified 5 primary themes: 1) Create easy-to-read documents through simplifying words and using visuals; 2) clearly communicate participation requirements in patient friendly terms, including an executive summary or table of logistical, financial, and patient reported outcomes requirements; 3) provide transparency: background on the treatment and personnel involved in study, explain the study’s privacy policies and what happens if the patient is no longer eligible for the trial; 4) provide supplemental information materials to aid understanding; 5) provide instructions for the investigator/trial team presenting the patient with the ICF. Conclusions: Feedback provided aligns with a recent proposal by the FDA to change existing regulations on informed consent to “facilitate a prospective [trial participant’s] decision about whether to participate in the research.” Findings from this analysis of patient advocate insights will be used to update the organization’s ICF template with improved comprehensibility of the form.
Levels of ANGPTL3 and characterization of other circulating cholesterol-related factors in high-grade serous ovarian cancers.
Authors: Emilie Yan Pin Wong Chong, France-Hélène Joncas, Pierre Douville, Dimcho Bachvarov, Ann-Charlotte Bergeron, Jonatan Blais, Nabil Georges Seidah, Frédéric Calon, Caroline Diorio, Anne Gangloff
Journal: Journal of Clinical Oncology (2023)

e17583 Background: Cancer cells require important amounts of cholesterol to sustain their growth. High-grade serous ovarian carcinomas (HGSOC), as an aggressive form of ovarian cancer, are no exception. Mechanisms allowing HGSOC to secure their lipid supplies are not yet fully elucidated. Recent years have highlighted ANGPTL3, PCSK9 and Apo CIII as key players in lipid metabolism. To date, impact of HGSOC on these key lipid-regulating factors is scantly documented. Herein, we compared ANGPTL3, PCSK9, Apo CIII and Lp(a) levels in women with HGSOC versus benign ovarian lesion (BOL) to better understand lipid metabolism in HGSOC. Methods: Plasma samples from 31 women with a HGSOC and 40 women with a BOL were assayed for ANGPTL3, PCSK9, and Apo CIII levels by ELISA. The lipid panel, Apo B and Lp(a) levels were measured on a Roche Modular analytical platform. Results: Higher levels of ANGPTL3 was observed in HGSOC (84 ng/ml, SD ±29 ng/ml, n = 31) vs. BOL (67 ng/ml, SD ±31 ng/ml, n = 40); HGSOC vs BOL p = 0.019. Receiver operating characteristic (ROC) curve analyses for ANGPTL3 combined with age indicated an area under curve of 67.7% (p = 0.005). Partial correlations indicated associations between the lipid panel and ANGPTL3, but only for BOL. Conclusions: In this cohort of 71 women, ANGPTL3 levels were higher in patients with HGSOC. This finding requires further validation in a larger cohort of HGSOC patients.
Surgical resection based on ontogenetic cancer field theory for cervical cancer: 10-year updated results of the MMR study.
Authors: Laura Weydandt, Benjamin Wolf, Nadja Dornhoefer, Bahriye Aktas
Journal: Journal of Clinical Oncology (2023)

5539 Background: Previously published findings from our center suggest that carcinoma of the cervix propagates within ontogenetic cancer fields, tissue compartments defined by staged morphogenesis. In the MMR study we aimed to determine whether surgical treatment that accounts for stage-associated, ontogenetic cancer fields and their associated lymphoid tissues results in locoregional tumor control without the need for adjuvant radiotherapy. Methods: The Leipzig School Mesometrial Resection Study (MMR study) is an ongoing, prospective, single-center, observational cohort study including patients with primary cervical cancer. All study participants undergo either total or extended mesometrial resection (TMMR or EMMR) and therapeutic lymph node dissection. Because this treatment strategy enables surgical removal of all locoregional at-risk tissues, no adjuvant radiotherapy is necessary, even in the presence of established risk factors. The trial is registered at the German Clinical Trials Register, number DRKS00015171. For this updated analysis, we identified patients in our institutional study database with primary cervical cancer staged IB1 – IIA2 according to the 2009 International Federation of Gynecology and Obstetrics staging system. Using the Kaplan-Meier estimator, we calculated recurrence free and overall survival. Results: Between October 16, 1999, and December 16, 2020, 420 patients were treated per protocol and followed up for a median of 136 months (IQR 77-190). The median age was 42 years (IQR 36-51). 329 patients (78.3%) had stage IB1, 58 (13.8%) stage IB2, 24 (5.7%) stage IIA1 and 9 (2.1%) stage IIA2 disease. Patients had either squamous cell (n = 297, 70.7%), adenocarcinoma (n = 104, 24.8%), adenosquamous (n = 18, 4.3%) or other (n = 1, 0.24%) histology. The nodal status was pN0 in 349 (83.1%) patients and pN1 in 71 (16.9%) of the cases. Clinically occult parametrial involvement was present in 47 (11.2%) patients. 10-year overall survival was 90.2% (95% confidence interval [CI] 87.1-93.4) and recurrence-free survival was 90.6% (95% CI 87.8-93.6). Stratified for lymph node status 10-year overall survival was 91.7% (95% confidence interval [CI] 88.5-95) for pN0 and 83.2% (95% confidence interval [CI] 74.6-92.9) for pN1. Recurrence-free survival was 93.8% (95% CI 91.2-96.5) for pN0 and 75.4% (95% CI 65.9-86.3) for pN1. Conclusions: Despite dispense of adjuvant radiotherapy, patients treated with total or extended mesometrial resection with therapeutic lymph node dissection have excellent survival outcomes. Additional multicenter studies are needed to further investigate and confirm our results. Clinical trial information: DRKS00015171 .
Early ctDNA reduction may identify patients with stable disease and long OS on tebentafusp.
Authors: Dan Feng, Laura Collins, Margaret K. Callahan, Ryan J. Sullivan, Sophie Piperno-Neumann, Paul D. Nathan, Jessica Cecile Hassel, Howard Goodall, Chris Holland, Koustubh Ranade, Alexander Noor Shoushtari
Journal: Journal of Clinical Oncology (2023)

9589 Background: Tebentafusp, a bispecific (gp100 × CD3) ImmTAC showed significant overall survival (OS) benefit (HR 0.51) versus investigator’s choice in a Phase (Ph) 3 trial in first line (1L) HLA-A*02:01+ adult patients (pts) with metastatic uveal melanoma (mUM) [Nathan NEJM 2021]. In Ph2 and Ph3 trials of tebentafusp, OS was improved regardless of RECIST best response and the degree of early reduction in ctDNA was a better predictor of OS [Carvajal Nat Med 2022; Sullivan AACR 2023]. Here we explored whether early on-treatment reduction in ctDNA could distinguish pts with stable disease (SD) and long OS vs those with SD and short OS in a Ph3 trial of tebentafusp in 1L mUM pts. Methods: 1L HLA-A*02:01+ pts with mUM received 68 mcg tebentafusp weekly intravenously after intra-patient dose escalation (NCT03070392). Response was assessed by investigators per RECISTv1.1. Sera collected at baseline (BL) and week 9 on tebentafusp were analyzed for ctDNA using targeted mPCR-NGS assay for mutations in 15 genes including GNAQ, GNA11, SF3B1, CYSLTR2, PLCB4 and EIF1AX. Landmark OS from week 9 was analyzed in subsets with ≥0-3 log reductions in mean tumor molecules (MTM) per ml of serum on treatment. Data cutoff 11-Nov-2022. Results: 76/245 (36%) tebentafusp-treated pts had best response of SD, with a median OS of 29 months and were evaluable for ctDNA. Baseline tumor burden as assessed by sum of longest lesion diameters and percentage of pts with elevated BL serum LDH were greater in the subset with &lt; 1 year (yr) OS (median 70 mm and 64%, respectively) than in subsets with OS ≥ 1 yr (median 42 mm, 11%) or OS ≥ 2 yrs (median 31 mm, 9%). Almost half (36/76; 47%) of all SD pts had detectable ctDNA mutations in one or more UM genes at baseline. Baseline ctDNA levels were similar across survival groups. By week 9 on-treatment, ctDNA reduction was observed in 34/36 (94%) evaluable SD pts, including 29/36 (81%) with ≥ 0.5 log reduction, 18/36 (50%) with ≥ 2 log reduction and 16/36 (44%) with undetectable ctDNA (clearance). Deeper reductions in ctDNA were associated with better OS (Table). Conclusions: In this Ph3 trial, ctDNA reduction by week 9 on tebentafusp was strongly associated with improved OS in pts with best RECIST SD. Early ctDNA reduction may predict SD patients with long OS on tebentafusp. [Table: see text]
Real world utilization and outcomes of immunotherapy regimens in metastatic castration resistant prostate cancer (mCRPC).
Authors: Teja Ganta, Jonathan Forrest Anker, Eric James Miller, Kai Tsao, William K. Oh
Journal: Journal of Clinical Oncology (2023)

e17038 Background: While immune checkpoint inhibitors (ICIs) have shifted the treatment paradigm in many cancers, their efficacy in mCRPC is limited. Ongoing research suggests distinct subpopulations of mCRPC may derive benefit or that combinatorial regimens including ICIs may overcome treatment resistance. This single-center retrospective study aims to describe real-world utilization patterns of ICIs for patients with mCRPC and assess the treatment effects. Methods: The EHR database was queried for patients with PC who were treated with an ICI outside of a clinical trial. Additional data were obtained from chart review and the cancer registry. Patients were excluded if ICI was given for another cancer type, non-metastatic disease, or as a component of small-cell lung cancer regimens. Kaplan-Meier curves were used to estimate time to events. Results: 31 patients are included in the study. From years 2016 to 2022, 13 patients received ICI alone. Starting in 2019, 18 patients received ICI combined with cabozantinib (C). ICI+C had PSA response rate (RR) of 50%, median duration of treatment (DOT) of 5.5 months, and median overall survival (OS) of 8 months (Table 1). 3 of these patients received therapy for ≥ 12 months. ICI alone had a RR of 0%. 94% of patients who received ICI+C were not a candidate for CONTACT-2 (NCT04446117). Conclusions: Oncologists continue to use ICI for mCRPC. While noncomparative, ICI+C demonstrated favorable activity over a historical cohort of ICI alone. Ongoing clinical trial participation is vital for patients with mCRPC; however, off-label prescribing may provide additional access to treatment options. [Table: see text]
The effect of maintenance hormone therapy on overall survival in advanced-stage low-grade serous ovarian carcinoma: A risk-set matched retrospective study.
Authors: Syem Barakzai, Amy Bregar, Marcela G. del Carmen, Eric L Eisenhauer, Annekathryn Goodman, Jose Alejandro Rauh-Hain, Allison Ann Gockley, Alexander Melamed
Journal: Journal of Clinical Oncology (2023)

5568 Background: Low-grade serous ovarian carcinoma (LGSOC) is a rare malignancy often treated similarly to high-grade serous ovarian carcinoma (HGSOC) despite differences in clinical behavior and carcinogenesis. Observational studies suggest that, among patient with advanced-stage LGSOC, maintenance hormonal therapy (HT) following primary treatment is associated with improved progression free survival. We conducted a multi-institutional observational study to investigate whether HT is associated with an overall survival advantage in this setting. Methods: We included patients with histologically confirmed stage III or IV LGSOC diagnosed between Jan 1, 2004, and Dec 31, 2019, treated in Commission on Cancer accredited cancer programs in the US. Patients who received HT within 6 months of diagnosis were matched to controls who did not initiate HT during this timeframe. The primary outcome was risk of death from any cause, within five-years of initiation of HT or observation. For each treated patient, we employed risk-set propensity score matching to identify a control in a manner that avoided the introduction of immortal-time-bias, and balanced groups with respect to year of diagnosis, upfront treatment strategy, age, stage, race/ethnicity, comorbidity index, insurance status, zip-code median income, and cancer program type. Results: There were 296 patients who initiated HT within 6 months of diagnosis, and 2,805 potential controls. Patients who received HT were more often treated in academic medical centers (55% vs 44%), diagnosed later in the study period (62% vs 23% diagnosed in 2018-2019), and received upfront chemotherapy less frequently (55% vs 83%). After risk set and propensity score matching, we identified 204 patients treated with HT and 204 untreated controls, who were otherwise similar with respect to measured covariates. In the matched cohort, maintenance HT was associated with a reduction in the risk of death (hazard ratio 0.61; 95% CI 0.37-0.99), corresponding to a 60-month survival of 71% compared with 61%, and an improvement in 5-year life expectancy of 3.6 months (95% CI 0.004-7.2). Conclusions: Maintenance hormone therapy following primary management of LGSOC is associated with an overall survival benefit compared with observation.
Quality of cancer family history taking in pediatric solid tumor patients.
Authors: Benjamin Hu, Danielle Kirkey, Molly McGuinness, Adrienne Wakeling, Sara R. Kreimer, Jacquelyn Crane, Arun A. Rangaswami, Sheri L. Spunt
Journal: Journal of Clinical Oncology (2023)

10045 Background: Approximately 10% of childhood solid tumors occur in individuals with a cancer genetic predisposition. Identifying cancer predisposition permits interventions for prevention and early detection of future cancers in the child and their affected family members and may have other important medical care implications. The American Society of Clinical Oncology (ASCO) guidelines recommend reviewing family history (FHx) to identify high-risk patients who should be offered genetic testing. To our knowledge, adherence to ASCO guidelines by pediatric oncology providers (POPs) has not been studied. Methods: Retrospective chart review of solid tumor patients &lt;18 years of age referred for genetic counseling 1/1/2017-1/31/2019. POP and genetic counselor (GC) FHx documentation was assessed for adherence with the ASCO minimum quality metrics: 2 generation pedigree, patient ethnicity, cancer genetic testing results in relatives (GTRR), and cancer type, age at diagnosis, and lineage (maternal/paternal) for each relative with cancer (RWC). Comparisons of FHx quality between POPs and GCs were evaluated with 1-sided t-tests. Ethnicity was considered assessed if both maternal and paternal ethnicities were documented. GTRR was considered assessed if the results of all relatives who had undergone genetic testing were noted. Cancer type, age at diagnosis, and lineage were considered assessed if they were checked for all RWCs. Whether or not the child underwent genetic testing and their testing results were also documented. Results: Of 129 eligible patients, 102 underwent germline genetic testing. Twelve (12%) had pathogenic alterations in cancer predisposition genes. The POP failed to document FHx in 20 patients (16%), including 2 with pathogenic germline alterations. The POP missed first/second degree RWCs in 32 of 88 patients with RWCs (36%). GCs achieved &gt;99% on each of the 6 ASCO quality metrics, whereas POPs performed significantly more poorly (Table). In patients with RWCs, GCs achieved all 6 metrics in more cases than POPs (99% vs. 3%, p&lt;0.001). Conclusions: POPs performed significantly worse than GCs in documenting family history compliant with ASCO minimum family history guidelines, raising concern for missed genetic cancer predisposition syndrome diagnoses in those not referred to a GC. Routine referral of pediatric solid tumor patients to a GC for family history review and interventions to improve the quality of family history taking by POPs may improve germline cancer predisposition detection, improving care of both patients and their affected family members. [Table: see text]
Biomarkers of response to sacituzumab govitecan (SG) and efficacy after treatment with enfortumab vedotin (EV) in advanced urothelial carcinoma (aUC): Analysis of the UNITE study.
Authors: Tanya Jindal, Cindy Jiang, Omar Alhalabi, Dimitra Rafailia Bakaloudi, Rafee Talukder, Matthew Davidsohn, Amanda Nizam, Amy K Taylor, Charles B Nguyen, Deepak Kilari, Cameron Pywell, Nancy B. Davis, Hamid Emamekhoo, Guru P. Sonpavde, Shilpa Gupta, Joaquim Bellmunt, Petros Grivas, Matthew T Campbell, Ajjai Shivaram Alva, Vadim S Koshkin
Journal: Journal of Clinical Oncology (2023)

4572 Background: SG is an antibody-drug conjugate (ADC) with accelerated FDA approval for aUC refractory to platinum-based chemotherapy and immune checkpoint inhibitor (ICI). SG activity following treatment with EV, the most commonly used ADC in the post-platinum/ICI setting, and biomarkers of response to SG are not well described. We hypothesized that SG would be active after EV in aUC. Methods: Patients (pts) treated with SG monotherapy who had next-generation sequencing (NGS), were identified in the retrospective UNITE study. Observed response rate (ORR) was determined for evaluable pts with scans after ≥1 SG cycle. All pts were assessed for baseline clinical characteristics, as well as molecular biomarkers including tumor mutational burden, somatic gene alterations (alt) in ≥ 10% of pts and presence of ≥1 DNA damage response (DDR) mutations. ORRs were compared with Chi-squared test. Kaplan Meier method and cox proportional hazard (cph) models were used to assess progression-free survival (PFS) and overall survival (OS) from SG start. Pt characteristics and molecular biomarkers were evaluated in univariate analyses (UVA), followed by evaluation of biomarkers in separate multivariate cph analyses (MVA), while accounting for clinical features. Results: Among 90 pts treated with SG at 9 US sites, 78 had NGS data. Median age at SG start was 68, 65 (72%) men, 73 (81%) Caucasian, 56 (62%) with pure urothelial histology, 60 (67%) primary bladder tumor and 67 (74%) ECOG PS 0/1. Most (n=84, 93%) received SG after EV, and 33 (37%) had ≥4 prior therapies for aUC. ORR with SG was 23% (15/66); 24% in pts with prior CR/PR/SD on EV and 14% after primary PD on EV. Median follow-up from SG start was 8.7 mos, PFS and OS were 3.5 mos and 7.1 mos. In pts with NGS, ORRs to SG were higher in MTAP altered pts (50% vs 19%; p = 0.05). In UVA, low neutrophil to lymphocyte ratio (NLR), high Hgb, no prior smoking history, &lt; 3 prior therapies, as well as BRCA2 and DDR alts were associated with longer OS (p&lt;0.05 for all). In MVA, pts with alt in either TP53 or MDM2 had longer OS. Conclusions: SG has notable activity after EV in heavily pretreated pts with aUC, with ORR consistent with SG phase 2 trial data in post-platinum/ICI only pts. We identified several clinical and genomic biomarkers, including TP53/MDM2 alt, that are potentially associated with improved outcomes with SG treatment. [Table: see text]
Multivariate index assay (MIA3G) to reduce preventive surgery for ovarian cancer.
Authors: Srinka Ghosh, Todd C. Pappas, Gerard P Reilly, Ryan Phan
Journal: Journal of Clinical Oncology (2023)

e17607 Background: Ovarian cancer (OC) – most lethal gynecologic malignancy - is rare among women with adnexal mass. Preventive adnexal surgery is a common practice, despite pathology confirming malignancy in only 10-15% of these cases. This motivates a surveillance-based clinical management paradigm to prognosticate the risk for malignancy and channel appropriately for surgery. We recently developed a multivariate index assay -MIA3G[1] - to assess risk for OC in women with adnexal mass. In a multi-center prospective surveillance trial, we assessed the concordance between preventive surgery and clinical management using MIA3G. Methods: MIA3G risk prediction uses a DNN algorithm which models 7 serum biomarkers (CA125, HE4, BM2, APO, FSH, TFR, PreAlbumin), age and menopausal status. With NPV of 99.7% (CI:99.2–99.9) it risk stratifies patients into low probability of malignancy or indeterminate. Across 11 centers, the MIA3G cohort comprised of 546 women (IQR:41-61yo) with symptomatic or asymptomatic masses and/or presence of HBOC variants. Serial blood draws were timed with clinic-visits and the ultimate one coincident with surgery. The objectives were: 1) prognosticate the MIA3G based preventive surgery pool and 2) establish concordance between the MIA3G probabilistic risk and the pathology-based outcome of malignancy versus benign. Results: In the study cohort of 546 patients, 20.3% (111) underwent preventive surgery. Conservatively, at a 12.8% FPR[1], MIA3G would have stratified approximately 70 patients, a projection of 37% less for surgery. Partitioning by clinical characteristic: (i) symptomatic: In comparison to 27.8% (73/263) of patients referred to surgery, MIA3G projections would have resulted in a 54.8%(33/263) reduction. (ii) asymptomatic: 22.5%(31/138) of patients were referred to surgery; MIA3G projections would have resulted in a 45.2% (17/138) reduction. In the 111 preventive surgeries, pathology confirmed a malignancy rate of 6.3% (7/111). The overall concordance of MIA3G with pathology was 84.68% (94/111) which increased to 91.98% (102/111) in the pre-menopausal (PRE) sub-cohort. The malignant discordancy (MIA3G:FN), all in PRE, comprised of early-stage epithelial: endometreoid, Leiomysarcoma and Sertoli-Leydig cell where the masses were characterized as cystic benign/indeterminate by ultrasound. These findings underscore the power of MIA3G when preventive surgery is considered for patients with ovarian cancer risk. Conclusions: The multivariate index assay MIA3G reduces numbers of preventative surgery for ovarian cancer risk. The high concordance establishes that MIA3G non-invasive surveillance-based clinical management can be effective for the risk assessment of ovarian cancer in patients presented with adnexal mass. Surgical management should be reserved for high probability of malignancy. [1]: DOI 10.3389/fmed.2023.1102437.